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Characterization of the Ascending Colon Fluids in Ulcerative Colitis
Authors:Maria Vertzoni  Konstantinos Goumas  Erik Söderlind  Bertil Abrahamsson  Jennifer B. Dressman  Androniki Poulou  Christos Reppas
Affiliation:1. Laboratory of Biopharmaceutics and Pharmacokinetics, National and Kapodistrian University of Athens, Athens, Greece
2. Red Cross Hospital of Athens, Athens, Greece
3. Pharmaceutical Development, AstraZeneca R&D, M?lndal, Sweden
4. Institute of Pharmaceutical Technology, Goethe University of Frankfurt, Frankfurt, Germany
5. Laboratory of Biopharmaceutics and Pharmacokinetics, Faculty of Pharmacy, National & Kapodistrian University of Athens, Panepistimiopolis, 157 71, Zografou, Greece
Abstract:

Purpose

To characterize the fluid composition in ascending colon of fasted adults with ulcerative colitis in relapse and in remission with a view to predicting variations on dosage form performance in the lower inflamed gut.

Methods

Twelve patients participated in a two-phase, crossover study. Enrolment to the relapse phase (Phase A) and designation of the remission state for the second colonoscopy (Phase B) were based on Clinical Rachmilewicz Index values. Samples were analyzed for pH and buffer capacity immediately upon collection. After ultracentrifugation, osmolality, surface tension, soluble protein, soluble carbohydrates, and the levels of ten bile acids, seven short-chain fatty acids (SCFAs), three long-chain fatty acids, triglycerides, diglycerides, monoglycerides, phosphatidylcholine, and cholesterol were measured.

Results

Total SCFAs are significantly decreased in relapse, but pH remains unaffected. Regardless of remission/relapse status, pH and isobutyric acid levels are lower than in healthy adults. Buffer capacity, osmolality, and soluble protein are higher than in healthy adults. Treatment with prednisolone increases the volume of intracolonic contents.

Conclusion

Variations in fluid composition of the ascending colon with activity and severity of ulcerative colitis may have an impact on the performance of orally administered products that are targeted to release the therapeutic agent in the colon.
Keywords:
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